Background/Purpose:

Foot disorders affect 2060% of adults and are often linked to physical limitations. Although genetics are commonly suspected in foot disorders, only two studies have been done: a family aggregation study showing that family history of hallux valgus may have an autosomal dominant transmission, and our work in 2010 that reported high heritability of hallux valgus and pes cavus. To our knowledge, no other studies have examined foot disorders and genetics in humans. Our purpose was to examine further heritability of several common foot conditions, linking data on specific foot disorders to a wealth of genetic data in the community-based Framingham Study, using their pedigree structure.

Methods:

The Framingham Foot Study (n=2179 participants examined in 20022005) was designed to examine common foot disorders and functional limitations. A trained examiner used a validated foot exam to assess specific foot disorders in participants. Genotyping has been obtained in 959 men and 1220 women. We estimated overall, sex-specific and age (< 60, 60+y) heritability of lesser toe deformities (hammer toes, claw toes, overlapping toes), heel fat-pad atrophy (present/absent), forefoot fat-pad atrophy (present/absent), and pes planus in the Framingham participants. Pes planus was defined using a digital recording of foot pressure while walking (MatScan device, Tekscan, Inc. Boston MA), that allowed calculation of the ratio of arch width (medial to lateral, to nearest 0.01 cm) to heel width. Pes planus (present/absent) was defined as either foot as having a weight-bearing arch width >= 75% of the heel width (previous work showed that this cut-point encompassed those with clinician impression of flat feet). We estimated heritability of the foot conditions by a standard quantitative genetic variance-components model implemented in the Sequential Oligogenic Linkage Analysis Routines (SOLAR) package.

Results:

Mean age was 66y (range 3999y); 57% were female. The prevalence of lesser toe deformities was 35% (753 toe deformity cases with available pedigree structure). The overall heritability of lesser toe deformities was 0.79 for women and 0.61 for men (both p-value < 0.01) and 0.56 for both sexes combined (p= 4 × 10-7) For persons aged < 60y, the heritability was 0.63. The prevalence of heel fat-pad atrophy was 13%, of forefoot fat-pad atrophy was 30%, and of pes planus was 8%. Of these foot conditions, none showed significant heritability overall or by group. Thus, only lesser toe deformities were highly heritable for both men and women.

Conclusion:

This study reveals new findings in an area that has received little attention, yet is critically important to general populations. We documented for the first time, the high heritability (strongly suspected by many) of a structural foot disorder phenotype: lesser toe deformities. As foot disorders are common, it is important to identify those at high risk, as effective interventions exist. Also, especially for lesser toe deformities, identification of individuals close to onset may lessen the impact of foot disorders or prevent development of physical limitations. Genome-wide association analyses are planned to identify potential genetic determinants for this common foot disorder.